RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by donor peripheral stem cell transplantation in treating patients who have mantle cell lymphoma.

Condition	Treatment or Intervention	Phase
Graft Versus Host Disease stage I mantle cell lymphoma contiguous stage II mantle cell lymphoma noncontiguous stage II mantle cell lymphoma stage III mantle cell lymphoma stage IV mantle cell lymphoma recurrent mantle cell lymphoma	Drug: allogeneic lymphocytes  Drug: carmustine  Drug: cytarabine  Drug: etoposide  Drug: melphalan  Drug: methotrexate  Drug: sargramostim  Drug: tacrolimus  Procedure: biological response modifier therapy  Procedure: bone marrow ablation with stem cell support  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: graft versus host disease prophylaxis/therapy  Procedure: leukocyte therapy  Procedure: peripheral blood lymphocyte therapy  Procedure: peripheral blood stem cell transplantation  Procedure: supportive care/therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the long term disease-free survival of patients with mantle cell lymphoma treated with etoposide, carmustine, melphalan, and cytarabine followed by allogeneic peripheral blood stem cell transplantation.
• Determine the incidence of molecular remissions in these patients treated with this regimen.
• Correlate the persistence of minimal residual disease with clinical outcome in these patients treated with this regimen.
• Determine the effect of donor lymphocytes in patients with progressive disease after treatment with this regimen.

OUTLINE: This is a multicenter study.

Patients receive carmustine IV over 2 hours on day -6; etoposide IV over 3 hours and cytarabine IV over 1 hour every 12 hours on days -5 to -2 for a total of 8 doses; and melphalan IV over 20-30 minutes on day -1. Patients undergo allogeneic peripheral blood stem cell (PBSC) transplantation on day 0. Patients also receive tacrolimus IV continuously over 24 hours beginning on day -2 and then orally twice daily until day 120 and methotrexate IV over 30 minutes on days 1, 3, and 6 as graft-versus-host disease (GVHD) prophylaxis. Patients receive sargramostim (GM-CSF) IV or subcutaneously daily beginning on day 7 and continuing until blood counts recover.

Patients with no active GVHD who have persistent disease on day 150 or progressive disease at any time after PBSC transplantation receive donor lymphocytes IV over 2 hours. Patients may receive additional donor lymphocytes at least 8 weeks later if disease persists.

Patients are followed at 6 and 12 months posttransplantation and then annually for 4 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 3.5 years.

Ages Eligible for Study:  up to  59 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed mantle cell lymphoma of any stage with at least 1 of the following:
• Immunophenotype with expression of CD5 and CD19 and absence of CD23
• Cytogenetic analysis with presence of t(11;14)
• Overexpression of cyclin D1
• Rearrangement of BCL1 gene
• Bone marrow biopsy required
• No needle or core biopsy as sole means of diagnosis
• First remission allowed if at least 1 of the following poor prognostic characteristics present:
• International Prognostic Index (IPI) score higher than 1 defined by the following risk factors:
• Performance status higher than 1
• Elevated LDH
• Presence of more than 1 extranodal site
• Stage III or IV disease
• Blastic variant of mantle cell lymphoma*
• Complex karyotypes (i.e., cytogenetic abnormalities different from or in addition to t(11;14)*
• Proliferative index more than 10%*
• Presence of p53 mutations NOTE: *Regardless of IPI score
• Failure of initial therapy with anthracycline-containing regimen allowed
• Failure to achieve clinical complete remission after initial therapy OR
• Recurrent disease after initial therapy
• HLA matched (6/6) sibling donor by serologic typing (A, B, or DR)
• Any age
• No syngeneic (identical twin) donor
• No active CNS lymphoma

PATIENT CHARACTERISTICS: Age:

• Under 60

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin less than 2 mg/dL
• AST and ALT no greater than 3 times upper limit of normal

Renal:

• Creatinine less than 2 mg/dL

Pulmonary:

• DLCO at least 40%
• No symptomatic pulmonary disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No prior bone marrow transplantation

Chemotherapy:

• See Disease Characteristics
• No more than 2 prior chemotherapy regimens
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy

Radiotherapy:

• No concurrent radiotherapy to bulky sites

Surgery:

• See Disease Characteristics

Alabama
      Veterans Affairs Medical Center - Birmingham, Birmingham,  Alabama,  35233-1996,  United States
California
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94143-0128,  United States
      University of California San Diego Cancer Center, La Jolla,  California,  92093-0658,  United States
      Veterans Affairs Medical Center - San Francisco, San Francisco,  California,  94121,  United States
Delaware
      CCOP - Christiana Care Health Services, Wilmington,  Delaware,  19899,  United States
District of Columbia
      Lombardi Cancer Center, Washington,  District of Columbia,  20007,  United States
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5000,  United States
Florida
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States
Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637-1470,  United States
      University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States
Iowa
      Holden Comprehensive Cancer Center, Iowa City,  Iowa,  52242-1009,  United States
Maine
      Veterans Affairs Medical Center - Togus, Togus,  Maine,  04330,  United States
Maryland
      Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      University of Massachusetts Memorial Medical Center - University Campus, Worcester,  Massachusetts,  01655,  United States
Minnesota
      University of Minnesota Cancer Center, Minneapolis,  Minnesota,  55455,  United States
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417,  United States
Missouri
      Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States
      Ellis Fischel Cancer Center - Columbia, Columbia,  Missouri,  65203,  United States
      Veterans Affairs Medical Center - Columbia (Truman Memorial), Columbia,  Missouri,  65201,  United States
Nebraska
      University of Nebraska Medical Center, Omaha,  Nebraska,  68198-7680,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
New Hampshire
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756-0002,  United States
New York
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., Syracuse,  New York,  13217,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      Mount Sinai Medical Center, NY, New York,  New York,  10029,  United States
      New York Presbyterian Hospital - Cornell Campus, New York,  New York,  10021,  United States
      North Shore University Hospital, Manhasset,  New York,  11030,  United States
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States
      State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States
      Veterans Affairs Medical Center - Buffalo, Buffalo,  New York,  14215,  United States
      Veterans Affairs Medical Center - Syracuse, Syracuse,  New York,  13210,  United States
North Carolina
      CCOP - Southeast Cancer Control Consortium, Winston Salem,  North Carolina,  27104-4241,  United States
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1082,  United States
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
      Veterans Affairs Medical Center - Durham, Durham,  North Carolina,  27705,  United States
Ohio
      Arthur G. James Cancer Hospital - Ohio State University, Columbus,  Ohio,  43210-1240,  United States
Rhode Island
      Rhode Island Hospital, Providence,  Rhode Island,  02903,  United States
Tennessee
      University of Tennessee Cancer Institute, Memphis,  Tennessee,  38103,  United States
      Veterans Affairs Medical Center - Memphis, Memphis,  Tennessee,  38104,  United States
Vermont
      Green Mountain Oncology Group, Bennington,  Vermont,  05201,  United States
      Vermont Cancer Center, Burlington,  Vermont,  05401-3498,  United States
      Veterans Affairs Medical Center - White River Junction, White River Junction,  Vermont,  05009,  United States
Virginia
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
      Veterans Affairs Medical Center - Richmond, Richmond,  Virginia,  23249,  United States

Study chairs or principal investigators

Koen Van Besien, MD,  Study Chair,  University of Illinois   

Study ID Numbers:  CDR0000068324; CLB-59908
Record last reviewed:  March 2003
Last Updated:  October 13, 2004
Record first received:  December 6, 2000
ClinicalTrials.gov Identifier:  NCT00006747
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08